Benzene Exposure Assessment Research Articles

Differences in exposure assignment between conception and delivery: the impact of maternal mobility

In studies of reproductive outcomes, maternal residence at delivery is often the only information available to characterise environmental exposures during pregnancy. The goal of this investigation was to describe residential mobility during pregnancy and to assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery. Maternal residential mobility was compared between neural tube defect cases and unaffected controls from Texas participants in the National Birth Defects Prevention Study (NBDPS). Maternal residential information was obtained from the NBDPS interview. Data from the U.S. EPA National Air Toxics Assessment [Assessment System for Population Exposure Nationwide (ASPEN)], modelled at the census tract level, were used to estimate benzene exposure based on address at conception and address at delivery. Quartiles of exposure were assigned based on these estimates and the quartile assignments based on address at conception and address at delivery were compared using traditional methods (kappa statistics) and a novel application of mixed-effects ordinal logistic regression. Overall, 30% of case mothers and 24% of control mothers moved during pregnancy. Differences in maternal residential mobility were not significant between cases and controls, other than case mothers who moved did so earlier during pregnancy than control mothers (P = 0.01). There was good agreement between quartiles of estimated benzene exposure at both addresses (kappa = 0.78, P < 0.0001). Based on the mixed-effects regression model, address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure based on estimates from ASPEN (odds ratio 1.03, 95% confidence interval 0.85, 1.25). Our results indicate that, in this Texas population, maternal residential movement is generally within short distances, is typically not different between cases and controls, and does not significantly influence benzene exposure assessment.

Maternal Personal Exposure to Airborne Benzene and Intrauterine Growth

BackgroundStudies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight.ObjectiveOur aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth.MethodsWe recruited pregnant women in two French maternity hospitals in 2005–2006 as part of the EDEN mother–child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth.ResultsMedian benzene exposure was 1.8 μg/m3 (5th, 95th percentiles, 0.5, 7.5 μg/m3). Log-transformed benzene exposure was associated with a gestational age–adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), −135 to −1 g] and of 1.9 mm in mean head circumference at birth (95% CI, −3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, −4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, −3.1 to 0 mm).ConclusionsOur prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.

Oxidative DNA damage and influence of genetic polymorphisms among urban and rural schoolchildren exposed to benzene

Traffic related urban air pollution is a major environmental health problem in many large cities. Children living in urban areas are exposed to benzene and other toxic pollutants simultaneously on a regular basis. Assessment of benzene exposure and oxidative DNA damage in schoolchildren in Bangkok compared with the rural schoolchildren was studied through the use of biomarkers. Benzene levels in ambient air at the roadside adjacent to Bangkok schools was 3.95-fold greater than that of rural school areas. Personal exposure to benzene in Bangkok schoolchildren was 3.04-fold higher than that in the rural schoolchildren. Blood benzene, urinary benzene and urinary muconic acid (MA) levels were significantly higher in the Bangkok schoolchildren. A significantly higher level of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in leukocytes and in urine was found in Bangkok children than in the rural children. There was a significant correlation between individual benzene exposure level and blood benzene ( r s = 0.193, P < 0.05), urinary benzene ( r s = 0.298, P < 0.05), urinary MA ( r s = 0.348 , P < 0.01), and 8-OHdG in leukocyte ( r s = 0.130, P < 0.05). In addition, a significant correlation between urinary MA and 8-OHdG in leukocytes ( r s = 0.241, P < 0.05) was also found. Polymorphisms of various xenobiotic metabolizing genes responsible for susceptibility to benzene toxicity have been studied; however only the GSTM1 genotypes had a significant effect on urinary MA excretion. Our data indicates that children living in the areas of high traffic density are exposed to a higher level of benzene than those living in rural areas. Exposure to higher level of benzene in urban children may contribute to oxidative DNA damage, suggesting an increased health risk from traffic benzene emission.

Exposure assessment of benzene in Thai workers, DNA-repair capacity and influence of genetic polymorphisms

Exposure to benzene can cause DNA damage and the subsequent development of cancer. In this study, study subjects were 31 laboratory workers at a petrochemical factory and 31 gasoline service attendants. Control subjects were 34 workers from a mail sorting service center. Occupational exposures to benzene were assessed using biomarkers of exposure in blood and urine. Induction of DNA-repair capacity was assessed as a biomarker of early effect. The effects of polymorphisms in a metabolizing gene ( CYP2E1), in detoxification genes ( NQO1 and GSTT1), and in a DNA-repair gene ( XRCC1, codon 399) on biomarker levels were evaluated. The mean individual benzene exposure of laboratory workers (24.40 ± 5.82 ppb) and that of gasoline service attendants (112.41 ± 13.92 ppb) were significantly higher than in controls (1.39 ± 0.17 ppb, p < 0.001). Blood benzene levels of laboratory workers (169.12 ± 30.60 ppt) and gasoline service attendants (483.46 ± 59.62 ppt) were significantly higher than those of the controls (43.30 ± 4.89 ppt, p < 0.001). Trans, trans-muconic acid levels in post-shift urine samples collected from laboratory workers (0.14 ± 0.02 mg/g creatinine) and gasoline service attendants (0.20 ± 0.02 mg/g creatinine) were significantly higher than in urine samples of controls (0.04 ± 0.01 mg/g creatinine, p < 0.001). The level of benzene exposure was correlated with blood benzene levels ( R 2 = 0.65, p < 0.01) and post-shift urinary trans, trans-muconic acid concentrations ( R 2 = 0.49, p < 0.01). As a biomarker of early effect, DNA-repair capacity was assessed by use of the cytogenetic challenge assay, i.e., chromosomal aberrations in peripheral lymphocytes were assessed after challenging blood cultures with 1 Gy gamma radiation. A significantly lower DNA-repair capacity – determined as dicentrics in laboratory workers (0.17 per metaphase cell) and in gasoline service attendants (0.19 per metaphase cell) compared with controls (0.12 per metaphase cell, p < 0.001) – was observed. The frequency of deletions in laboratory workers (0.22 per metaphase cell) and gasoline service attendants (0.39 per metaphase cell) were significantly higher than in control workers (0.16 per metaphase cell, p < 0.01 and p < 0.001, respectively). An increase in radiation-induced dicentrics and deletions indicate a lower DNA-repair capacity in benzene-exposed workers. The influence of genetic polymorphisms on the biomarkers was assessed. Benzene-exposed workers who carried CYP2E1*1/*5 or *5/*5 genotypes excreted slightly higher levels of trans, trans-muconic acid than workers who carried the CYP2E1*1/*1 genotype. In this study, NQO1 and GSTT1 genotypes did not have any effect on the levels of trans, trans-muconic acid. In the case of XRCC1, laboratory workers with 399Arg/Gln or Gln/Gln had a lower DNA-repair capacity – measured as radiation-induced frequency of dicentrics and deletions – than those with the 399Arg/Arg genotype ( p < 0.01). Our results show that biomarkers of internal dose and early biological effect in people occupationally exposed to benzene are influenced by genetic polymorphisms in susceptibility genes.

Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China.

We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (< or =5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation.

Benzene exposure assessment for use of a mineral spirits-based degreaser.

This study examines benzene emissions from the use of a metal parts washer ("degreaser") supplied with a mineral spirits solvent containing either 9 or 58 ppm benzene. Air samples were obtained during a one-hour session of relatively vigorous parts cleaning activity using a degreaser station equipped with wet brush and sprayer attachments and a compressed air hose. Two methods were utilized to assess airborne benzene levels: U.S. EPA TO-14 (summa stainless steel canister) and NIOSH 1501 (charcoal tube). Overall, both methods provided similar results, excepting detection limit differences. The first simulation was performed with recycled solvent (9 ppm benzene in solvent) showing average one-hour airborne benzene levels < or =33 ppbv in the worker's breathing zone and directly above the parts cleaning tank. Average airborne benzene concentrations 18 inches away from the tank were below 2 ppbv during the 60-minute cleaning protocol. The second simulation with benzene-spiked recycled solvent (58 ppm benzene) showed airborne benzene levels averaging 500 ppbv measured over the 60-minute cleaning period in the worker's breathing zone and directly above the tank, while average concentrations 18 inches from the tank perimeter were 63 ppbv. The data indicate that average and peak exposures to airborne benzene were roughly proportional to the solvent benzene content, although the brief peak exposures exhibited greater variance probably related to aerosol generation associated with the use of the brush and/or spraying attachment. Under this selected upper bound exposure simulation, we found that cleaning parts using a recycled mineral spirits-based solvent in an open warehouse setting did not result in exposures in excess of the current occupational exposure limit of 0.5 ppm averaged over 8 hours for solvent benzene content between 9 and 58 ppm.

Environmental benzene exposure assessment for parent–child pairs in Rouen, France

There is a lack of data on environmental benzene exposure in children. In this study, we compared personal benzene exposure and inhalation uptake in a group of children to those of their parents. We also compared levels of urinary benzene metabolites, trans,trans-muconic acid (MA) and hydroquinone (HQ), for those two groups, and assessed the correlation between personal benzene exposure and urinary MA and HQ concentrations. The study was performed on 21, 2–3-year-old children and their parents recruited on a voluntary basis among non-smokers from the three largest day-care centers of the town of Rouen in France. Average benzene concentrations were measured over 5 consecutive days with diffusive samplers. The following simultaneous measurements were carried out: personal exposure of the parents, concentrations inside and outside the day care centers, and inside the volunteer's bedrooms. Morning and evening urine samples were collected during the same period. Benzene personal exposure levels were 14.4±7.7 μg/m 3 and 11.09±6.15 μg/m 3 in parents and children, respectively. Benzene inhalation uptake estimates were 2.51±1.23 μg/kg/day in the group of parents and 5.68±3.17 μg/kg/day in the group of children. Detectable levels of MA and HQ were found in 85% and 100% of the samples, respectively. Intra-individual variation of urinary MA and HQ concentrations expressed as a coefficient of variation (CV) ranged from 63 to 232% and from 13 to 144%, respectively. Mean values of MA and HQ (in mg/g creatinine) were 1.6- and 1.8-fold higher in the group of children than in the group of parents ( P=0.008 and P<0.0001, respectively). Significant correlations between metabolites levels and benzene were not found.

Use of expert judgment in exposure assessment. Part I. Characterization of personal exposure to benzene.

This paper presents the results of the first phase of a study, conducted as an element of the National Human Exposure Assessment Survey (NHEXAS), to demonstrate the use of expert subjective judgment elicitation techniques to characterize the magnitude of and uncertainty in environmental exposure to benzene. In decisions about the value of exposure research or of regulatory controls, the characterization of uncertainty can play an influential role. Classical methods for characterizing uncertainty may be sufficient when adequate amounts of relevant data are available. Frequently, however, data are neither abundant nor directly relevant, making it necessary to rely to varying degrees on subjective judgment. Since the 1950s, methods to elicit and quantify subjective judgments have been explored but have rarely been applied to the field of environmental exposure assessment. In this phase of the project, seven experts in benzene exposure assessment were selected through a peer nomination process, participated in a 2-day workshop, and were interviewed individually to elicit their judgments about the distributions of residential ambient, residential indoor, and personal air benzene concentrations (6-day integrated average) experienced by both the non-smoking, non-occupationally exposed target and study populations of the US EPA Region V pilot study. Specifically, each expert was asked to characterize, in probabilistic form, the arithmetic means and the 90th percentiles of these distributions. This paper presents the experts' judgments about the concentrations of benzene encountered by the target population. The experts' judgments about levels of benzene in personal air were demonstrative of patterns observed in the judgments about the other distributions. They were in closest agreement about their predictions of the mean; with one exception, their best estimates of the mean fell within 7-11 microg/m(3) although they exhibited striking differences in the degree of uncertainty expressed. Their estimates of the 90th percentile were more varied with the best estimates ranging from 12 to 26 microg/m(3) for all but one expert. However, their predictions of the 90th percentile were far more uncertain. The paper demonstrates that coherent subjective judgments can be elicited from exposure assessment scientists and critically examines the challenges and potential benefits of a subjective judgment approach. The results of the second phase of the project, in which measurements from the NHEXAS field study in Region V are used to calibrate the experts' judgments about the benzene exposures in the study population, will be presented in a second paper.

Validation of benzene exposure assessment.

We conducted a methodologic study to validate a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work-unit/job-title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures occurred in the rubber industry (30.7 ppm), particularly for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning (hematotoxicity) and benzene exposure was evaluated (412 cases and 614,509 person-years) to validate the exposure-assessment method. Relative risks of benzene hematotoxicity increased very sharply with increasing estimated intensity of benzene exposure. Odds ratios were 2.2 (95% CI: 1.7-2.9), 4.7 (95% CI: 3.4-6.5), and 7.2 (95% CI: 5.3-9.8) for the intensity levels of less than 5 ppm, 5-19 ppm, 20-39 ppm, and 40 and more ppm, respectively. This sharp trend between benzene hematotoxicity and estimated exposure to benzene indicated that the exposure-estimation method used in this cancer epidemiology study is reliable.

The Specificity of trans,trans- Muconic Acid as a Biological Indicator for Low Levels of Environmental Benzene

trans, trans -Muconic acid (MA), a urinary ring-opened metabolite of benzene, is a newly proposed biological indicator of benzene exposure which should enable the assessment of low levels of exposure to this ubiquitous environmen tal pollutant. The presence of MA in the urine of non-occupationally exposed people is generally attributed to world-wide contamination of the environ ment by benzene (arising from such sources as smoking and other combustion, urban pollution from vehicles and maybe by food contamination). But, exami nation of the scientific literature reveals that a common food preservative and fungistatic agent, sorbic acid (SA), is also converted into MA, although in trace amounts. The permitted maximum concentration of SA in food ranges from 0.2 to 2 g·kg -1 and the acceptable daily intake (ADI-FAO/WHO) is 25 mg. kg -1 of body weight. The question, therefore, is whether the amount of MA excreted as a metabolite of SA can make a significant contribution to the total MA excreted. If so, the specificity of MA as a biological indicator for benzene exposure assessment is in doubt. Four experiments in 2 subjects were set up to try to clarify the effect on the urinary excretion of MA of the experimental ingestion of SA (2 doses of 447 and 44.7 mg); urine samples were collected, in fractions as voided, for 24 h before and 48 (or 60 h) after SA ingestion. The total amounts of MA excreted during the 24 h before ingestion of SA were respectively 79 and 34 mg in the 2 subjects; after ingestion of 447 or 44.7 mg of SA the total excretion of MA was at least respectively 20 and 2 times the background levels (when the single dose of SA was ingested) and at least 10 and 3 times (when the SA was given in divided doses). The elimination of MA after ingestion of SA was complete in 24 h; the peak concentrations always appeared in the first urine sample after the ingestion of the substance and they were more than 90 times and more than 3 times the basal levels respectively for a single ingestion of 447 and 44.7 mg of SA. The rate of biotransformation of SA into MA was, on average, 0.34 and 0.21 % in the 2 subjects; on the basis of these levels of biotransformation, it appears that 0.3-0.5 g of ingested SA would suffice to lead to excretion of 1 mg of MA, a quantity corresponding to that believed to derive from benzene exposure at levels greater than 1 ppm. Only in urine collected many hours after the last meal can a possible additive effect of MA from SA be ignored.

Indirect Validation of Benzene Exposure Assessment by Association with Benzene Poisoning

Indirect Validation of Benzene Exposure Assessment by Association with Benzene Poisoning

Indirect validation of benzene exposure assessment by association with benzene poisoning.

We present a validation study of a quantitative retrospective exposure assessment method used in a follow-up study of workers exposed to benzene. Assessment of exposure to benzene was carried out in 672 factories in 12 cities in China. Historical exposure data were collected for 3179 unique job titles. The basic unit for exposure assessment was a factory/work unit/job title combination over seven periods between 1949 and 1987. A total of 18,435 exposure estimates was developed, using all available historical information, including 8477 monitoring data. Overall, 38% of the estimates were based on benzene monitoring data. The highest time-weighted average exposures were observed for the rubber industry (30.7 ppm) and for rubber glue applicators (52.6 ppm). Because of its recognized link with benzene exposure, the association between a clinical diagnosis of benzene poisoning and benzene exposure was evaluated to validate the assessment method that we used in the cohort study. Our confidence in the assessment method is supported by the observation of a strong positive trend between benzene poisoning and various measures, especially recent intensity of exposure to benzene.

Benzene exposure assessment in rubber hydrochloride workers: A critical evaluation of previous estimates

Many risk assessments for leukemia associated with benzene exposure have been based on the mortality experience of the rubber hydrochloride worker cohort. Although there have been several different historical exposure assessments proposed for this cohort, Paustenbach et al. [1992, J Tox Environ Health], recently published a new historical characterization of benzene exposures based on data previously developed by Rinsky et al. [1981, Am J Ind Med] and further modified by Crump and Allen [1984: OSHA]. Adjustments by Paustenbach et al. in the Rinsky et al. data result in retrospective benzene exposure estimates far greater than those previously reported, by an order of magnitude in many cases. Judgments made on the significance of dermal contact and interpretation of historical measurement data led Paustenbach et al. to arrive at exposure estimates for this cohort that are in conflict with what is known about the adverse effects of benzene exposure. More reasonable estimates for dermal absorption are included in this report that do not substantially affect total estimates of benzene exposure for the cohort. The exposure estimates originally presented in the Rinsky et al. article appear in concordance with data not previously reported in any analyses.

A microassay for urinary phenol using capillary gas chromatography and optimised enzymic hydrolysis

An improved capillary gas chromatography method is described for the assay of urinary phenol for the assessment of benzene exposure. Enzymatic hydrolysis with an extract of Helix pomatia is used to liberate phenol from its glucuronide and sulphate conjugates in urine and has the advantage in that complete hydrolysis occurs and clean chromatograms are produced. Furthermore, an internal standard (2,4-xylenol) has been incorporated in the method enabling rapid and single step extraction of phenol. The microassay can be used to measure phenol concentrations as low as 1 mg/l in urine thus making it a suitable method for monitoring benzene exposure.

Improvement in HPLC analysis of urinary trans, trans-muconic acid, a promising substitute for phenol in the assessment of benzene exposure

Urinary trans,trans-muconic acid (t,t-MA), a minor metabolite of benzene, is a potential candidate for biological monitoring of benzene. A clean-up procedure using SPE extraction cartridges was applied to urinary samples in order to improve the reliability of t,t-MA determinations by HPLC-UV greatly and to carry out convenient analyses on a routine scale, particularly at low levels of t,t-MA concentrations. The detection limit of the method is low enough to measure urinary t,t-MA at a concentration of 0.05-0.1 mg/l. The recovery rates and relative standard deviations from spiked urines (1 mg/l to 20 mg/l) were about 90% and 5%, respectively. t,t-MA was found to be rapidly excreted by rats and humans. In rats the background range never exceeded 0.5 mg/l with a mean concentration around 0.3 mg/l. In 49 human blank urines, t,t-MA average and median-value were respectively around 0.2 and less than 0.1 mg/l with a range of less than 0.1 to 0.5 mg/l. Experimental exposure of rats for 1 h to 10.2 ppm of benzene induced urinary excretion of 13 mg/l of t,t-MA during a 6-h post-exposure period while occupational exposures to 2.6 ppm (mean exposure level during 5 d-8 h) and 7 ppm (4 h) of benzene resulted in urinary excretion of 2.1 (mean excretion level) and 6.5 mg/l respectively at the end of the exposure. In humans, t,t-MA has a similar half-time as phenol. Analysis of urinary t,t-MA seems to be a better indicator than phenol for the assessment of exposure to low levels of benzene. Ingestion of 200 mg of sorbic acid, the only other known precursor of t,t-MA, interfered minimally with the background excretion of t,t-MA.

Benzene Exposure Assessment of Underground Storage Tank Contractors

Abstract Benzene and total hydrocarbon (as hexane) exposures were measured during removal, cleaning, pumping, and testing of underground gasoline storage tanks at five gasoline retail outlets in New Jersey during 1988. Personal air samples were collected using 3M 3500 Organic Vapor Monitors with sampling times ranging from 15 minutes to 6.5 hours. Benzene exposures to the observer ranged from 0.12 to 0.43 ppm (sampling times ranging from 4.75 to 6.5 hours). Benzene exposures to laborers during tank removal (including cutting and cleaning) ranged from 0.43 to 3.84 ppm (sampling times ranging from 1.5 to 6 hours). The highest short-term benzene exposure was 9.14 ppm (sampling time 15 minutes) for a tank cleaning assistant. Benzene exposures during tank cutting ranged from 2.16 to 4.57 ppm (sampling times ranged from 0.5 to 3 hours). Benzene exposure to a tank tester was 0.23 ppm (sampling time of 4.75 hours). Total hydrocarbons as hexane were also determined. The mean ratio of benezene to total hydrocarbon concentrations was 0.028 (n = 21, S.D. 0.02). Gasoline tanks were not purged of vapors prior to being removed, cut open, and cleaned. This raises a safety issue (flammable/combustible vapor hazard) in addition to changing the time, duration, and magnitude of benzene exposure during the tank removal process. Dermal exposure to gasoline was frequent.